Should very preterm infants be given higher initial oxygen levels?

Contrary to existing recommendations, resuscitating extremely preterm babies with initial high-concentration oxygen in the delivery room may reduce their chances of death, suggests a systematic review and individual participant data network meta-analysis.

Using data from 12 randomized trials and over 1,000 infants under 32 weeks of gestation, the authors found that high initial fraction of inspired oxygen (FiO₂) was associated with a 55% reduction in mortality (OR 0.45, 95% CI 0.01–0.25). [CrI] Compared to a lower FiO of 0.23-0.86₂ Less than 30%, but the certainty of the evidence is low.

Furthermore, its high initial FiO₂ It was also associated with lower mortality compared with moderate FiO.₂ 50% to 65% (OR 0.34 95% CrI 0.11-0.99)), This time, the certainty of the evidence is very low, reported Dr. James Sotiropoulos, MD, of the University of Sydney in Australia, and his colleagues.

The findings differ from current recommendations and call for further evaluation of high initial FiO.₂ The researchers: JAMA Pediatrics.

“Although promising and potentially practice-changing, these findings need to be confirmed in future larger studies,” Sotiropoulos said. press release.

The number of people needed to treat to avoid one additional death was 16 when comparing high oxygen vs. low oxygen, and 11 when comparing high oxygen vs. moderate oxygen.

“Making sure that extremely premature babies get the right treatment from the beginning can help them live healthy lives,” he said. “The goal is to find the right balance – how to give them enough oxygen to prevent death or disability, but not damage their vital organs.”

Historically, FiO₂ In their introduction, the study authors explain that 100% room air was used for all infants requiring resuscitation at birth, until more recent data showed an association of room air with reduced mortality among term and near-term infants, resulting in a change in practice.

“As a result, International Treatment Recommendations “In 2010, we recommended the judicious use of mixed oxygen in preterm infants, despite the lack of conclusive evidence for this vulnerable population,” Sotiropoulos and colleagues wrote.

For preterm infants, who often require supplemental oxygen to prevent hypoxia, these guidelines recommend low oxygen concentrations (FiO₂ 21% to 30%, then oxygen saturation (SpO₂) goals are 80% to 85% after five minutes of survival and 85% to 95% after 10 minutes, they noted.

Still, the researchers urged caution in interpreting their results, given the large amount of evidence that high oxygen levels can cause harm.

“Excessive exposure to oxygen increases the formation of harmful reactive oxygen species, which can cause irreversible damage to organs and tissues,” Sotiropoulos and his co-authors write.

“Thus, the benefits of increased oxygen concentrations must be balanced against the potential risks of hyperoxia,” the researchers continued. “SpO₂ Titration of FiO₂However, overuse of high concentrations of oxygen may be harmful. Our findings do not support the conventional practice of administering a static concentration of 100% oxygen, but rather the use of a high initial FiO₂ Subsequent titration to the lowest effective oxygen dose may be superior to starting at a low FiO.₂ And then titrate and increase.”

For their study, Sotiropoulos and his colleagues included 12 randomized trials conducted between 2005 and 2019 that compared two or more initial oxygen concentrations for delivery room resuscitation, ultimately including individual patient data for 1,055 infants under 32 weeks' gestation.

Ten of the studies were conducted in high-income countries and two in middle-income countries; studies with low or moderate initial FiO₂ This is permitted if oxygen concentrations are adjusted based on clinical status.

Of the infants included, 48% were girls and the mean gestational age was 28 weeks. The mean birth weight was 1.1 kg, about two-thirds were delivered by Caesarean section, 17% were multiple pregnancies, and 10% were small for gestational age. Most infants received hypoxia (n=507) followed by hyperoxia (n=378) or moderate oxygen (n=170).

The primary endpoint was mortality, and across the 11 studies (n=1,003) that contributed to this endpoint, deaths occurred in 12%. The researchers reported that “when examining treatment-covariate interactions, there was no evidence of differences in treatment effect by gestational age or infant sex (post-hoc, primary endpoints only),” but noted that the power to detect such interactions was limited.

No differences were found between the different initial oxygen concentrations for the secondary outcomes of chronic lung disease, severe intraventricular hemorrhage, and retinopathy of prematurity (based on 11 trials).

Nine studies provided data on oxygen saturation outcomes, with infants receiving higher initial oxygen concentrations having lower SpO₂ At 5 minutes, SpO of at least 80% was associated with lower initial oxygen (OR 3.67, 95% CrI 1.15-12.21) compared with lower initial oxygen (OR 3.23, 95% CrI 1.21-12.22).₂ The value after 5 minutes was 9.02 (95% CrI 2.08-16.31), favoring a higher initial oxygen concentration over a lower one.

Limitations include high risk of bias in the studies (three studies for the primary endpoint) mainly due to inadequate blinding, and low-certainty evidence due to the small number of death events. Sotiropoulos and her co-authors also noted that few infants were born before 24 weeks' gestation, limiting generalizability to this group.